{"gene":"SAMD12","run_date":"2026-04-28T20:42:06","timeline":{"discoveries":[{"year":2018,"finding":"Intronic TTTCA and TTTTA pentanucleotide repeat expansions in intron 4 of SAMD12 are the causative mutations for familial cortical myoclonic tremor with epilepsy (FCMTE/BAFME1), identified by long-read sequencing and validated by repeat-primed PCR with co-segregation in affected pedigrees.","method":"Long-read sequencing (PacBio/Oxford Nanopore), repeat-primed PCR, long-range PCR, co-segregation analysis","journal":"Journal of medical genetics","confidence":"High","confidence_rationale":"Tier 2 — independently replicated across multiple labs and populations (Chinese, Japanese) with multiple orthogonal methods","pmids":["30194086","29939203","30559482"],"is_preprint":false},{"year":2025,"finding":"SAMD12 protein binds to CNKSR1/2/3 scaffold proteins with exceptionally strong affinity and competitively displaces MAP4K kinases (MAP4K4, MINK1, TNIK) from CNKSR1/2/3 scaffolds, thereby decoupling these kinases from their scaffold and inhibiting TNIK activity; ectopic expression of SAMD12 alters neuronal synapse development through this mechanism.","method":"Protein interaction characterization (binding affinity measurements), competitive displacement assays, ectopic expression with synapse development readout","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 — single lab with multiple biochemical methods and functional cellular readout, but not yet independently replicated","pmids":["40010432"],"is_preprint":false},{"year":2025,"finding":"CNKSR2 acts as both a scaffold and an activator of TNIK during neuronal synapse development, and SAMD12 can inhibit TNIK activity by dissociating TNIK from the CNKSR2 complex.","method":"Biochemical interaction assays, ectopic expression, synapse development functional assays","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 — single lab with multiple orthogonal methods demonstrating mechanistic pathway placement","pmids":["40010432"],"is_preprint":false},{"year":2023,"finding":"miR-106a-5p derived from liver fibrosis exosomes targets SAMD12, and knockdown of SAMD12 in liver cancer cell lines exacerbates cell proliferation, indicating SAMD12 suppresses hepatocellular carcinoma cell growth.","method":"In vitro knockdown with proliferation assay, in vivo validation","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 — single lab, KD with cellular phenotype but limited mechanistic pathway detail for SAMD12 protein itself","pmids":["37228062"],"is_preprint":false},{"year":2021,"finding":"The SAMD12 TTTCA/TTTTA repeat expansion mutant allele is unstable and can undergo both contraction and expansion upon intergenerational transmission, with allele sizes varying in repeat copy number between generations.","method":"PacBio sequencing of long-range PCR products, repeat-primed PCR","journal":"Epilepsia open","confidence":"Medium","confidence_rationale":"Tier 2 — direct sequencing of alleles across generations demonstrating instability","pmids":["33681653"],"is_preprint":false}],"current_model":"SAMD12 is a sterile alpha motif domain-containing protein whose intronic TTTCA/TTTTA pentanucleotide repeat expansion causes familial adult myoclonic epilepsy (BAFME1/FCMTE1); at the protein level, SAMD12 functions as a master regulator of MAP4K kinases (TNIK, MINK1, MAP4K4) by binding CNKSR1/2/3 scaffold proteins with high affinity, competitively displacing MAP4Ks from these scaffolds to inhibit kinase activity and thereby modulate neuronal synapse development."},"narrative":{"teleology":[{"year":2018,"claim":"The genetic basis of BAFME1/FCMTE1 was resolved: intronic pentanucleotide repeat expansions in SAMD12 were identified as the causative mutations, establishing this gene as the disease locus after years of linkage studies had narrowed the interval.","evidence":"Long-read sequencing (PacBio/Nanopore), repeat-primed PCR, and co-segregation analysis across multiple affected pedigrees in Chinese and Japanese cohorts","pmids":["30194086","29939203","30559482"],"confidence":"High","gaps":["Whether pathogenesis is driven by RNA toxicity from repeat transcripts, loss of SAMD12 protein function, or both remains unresolved","No mechanism linking the repeat expansion to cortical myoclonus or epileptogenesis was established"]},{"year":2021,"claim":"The SAMD12 repeat expansion was shown to be meiotically unstable, undergoing both contraction and expansion across generations, providing a molecular basis for variable clinical severity and anticipation observed in BAFME1 families.","evidence":"PacBio sequencing of long-range PCR products across parent-offspring transmissions","pmids":["33681653"],"confidence":"Medium","gaps":["The relationship between repeat length and disease severity or age of onset was not quantitatively defined","Somatic mosaicism of repeat length in brain tissue has not been characterized"]},{"year":2025,"claim":"The first protein-level function of SAMD12 was established: it acts as a competitive inhibitor of MAP4K kinase–scaffold interactions by binding CNKSR1/2/3 with high affinity and displacing TNIK/MINK1/MAP4K4, with functional consequences for neuronal synapse development.","evidence":"Binding affinity measurements, competitive displacement assays, and ectopic expression with synapse development readouts in a single-lab study","pmids":["40010432"],"confidence":"Medium","gaps":["Independent replication of the SAMD12–CNKSR competitive displacement mechanism has not been reported","Whether SAMD12 loss-of-function (as might occur from repeat expansion) dysregulates TNIK signaling in patient neurons is untested","Structural basis of the high-affinity SAMD12–CNKSR interaction is unknown"]},{"year":null,"claim":"A critical open question is whether the BAFME1-associated repeat expansion causes disease through loss of SAMD12 protein function (and consequent derepression of MAP4K/TNIK signaling), RNA gain-of-function toxicity, or a combination of both mechanisms.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No animal model recapitulating both the repeat expansion and BAFME1 phenotype has been reported","SAMD12 protein levels and TNIK activity have not been measured in patient-derived neurons","The endogenous expression pattern of SAMD12 in human brain regions relevant to BAFME1 is poorly characterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,2]}],"localization":[],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["CNKSR1","CNKSR2","CNKSR3","TNIK","MINK1","MAP4K4"],"other_free_text":[]},"mechanistic_narrative":"SAMD12 is a sterile alpha motif domain-containing protein that functions as a negative regulator of MAP4K kinase signaling at neuronal synapses. SAMD12 binds CNKSR1/2/3 scaffold proteins with high affinity and competitively displaces MAP4K kinases (MAP4K4, MINK1, TNIK) from these scaffolds, thereby inhibiting TNIK activity and modulating synapse development [PMID:40010432]. Intronic TTTCA and TTTTA pentanucleotide repeat expansions in SAMD12 cause familial cortical myoclonic tremor with epilepsy (BAFME1/FCMTE1), with the expanded repeat alleles exhibiting intergenerational instability [PMID:30194086, PMID:33681653]."},"prefetch_data":{"uniprot":{"accession":"Q8N8I0","full_name":"Sterile alpha motif domain-containing protein 12","aliases":[],"length_aa":201,"mass_kda":22.9,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8N8I0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SAMD12","classification":"Not Classified","n_dependent_lines":9,"n_total_lines":1208,"dependency_fraction":0.0074503311258278145},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SAMD12","total_profiled":1310},"omim":[{"mim_id":"618075","title":"EPILEPSY, FAMILIAL ADULT MYOCLONIC, 7; FAME7","url":"https://www.omim.org/entry/618075"},{"mim_id":"618074","title":"EPILEPSY, FAMILIAL ADULT MYOCLONIC, 6; FAME6","url":"https://www.omim.org/entry/618074"},{"mim_id":"618073","title":"STERILE ALPHA MOTIF DOMAIN-CONTAINING PROTEIN 12; SAMD12","url":"https://www.omim.org/entry/618073"},{"mim_id":"610739","title":"TRINUCLEOTIDE REPEAT-CONTAINING GENE 6A; TNRC6A","url":"https://www.omim.org/entry/610739"},{"mim_id":"609530","title":"RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 2; RAPGEF2","url":"https://www.omim.org/entry/609530"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SAMD12"},"hgnc":{"alias_symbol":["FLJ39458"],"prev_symbol":[]},"alphafold":{"accession":"Q8N8I0","domains":[{"cath_id":"1.10.150.50","chopping":"75-158_172-198","consensus_level":"medium","plddt":89.3864,"start":75,"end":198}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8I0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8I0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N8I0-F1-predicted_aligned_error_v6.png","plddt_mean":71.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SAMD12","jax_strain_url":"https://www.jax.org/strain/search?query=SAMD12"},"sequence":{"accession":"Q8N8I0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N8I0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N8I0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N8I0"}},"corpus_meta":[{"pmid":"30194086","id":"PMC_30194086","title":"Long-read sequencing identified intronic repeat expansions in SAMD12 from Chinese pedigrees affected with familial cortical myoclonic tremor with epilepsy.","date":"2018","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30194086","citation_count":80,"is_preprint":false},{"pmid":"29939203","id":"PMC_29939203","title":"Intronic pentanucleotide TTTCA repeat insertion in the SAMD12 gene causes familial cortical myoclonic tremor with epilepsy type 1.","date":"2018","source":"Brain : a journal of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/29939203","citation_count":76,"is_preprint":false},{"pmid":"30559482","id":"PMC_30559482","title":"Detecting a long insertion variant in SAMD12 by SMRT sequencing: implications of long-read whole-genome sequencing for repeat expansion diseases.","date":"2018","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30559482","citation_count":38,"is_preprint":false},{"pmid":"31406141","id":"PMC_31406141","title":"LncRNA SAMD12-AS1 promotes cell proliferation and inhibits apoptosis by interacting with NPM1.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31406141","citation_count":27,"is_preprint":false},{"pmid":"32203200","id":"PMC_32203200","title":"Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families.","date":"2020","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/32203200","citation_count":25,"is_preprint":false},{"pmid":"33962804","id":"PMC_33962804","title":"LncRNA SAMD12-AS1 Promotes the Progression of Gastric Cancer via DNMT1/p53 Axis.","date":"2021","source":"Archives of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/33962804","citation_count":22,"is_preprint":false},{"pmid":"32973343","id":"PMC_32973343","title":"Founder effect of the TTTCA repeat insertions in SAMD12 causing BAFME1.","date":"2020","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/32973343","citation_count":16,"is_preprint":false},{"pmid":"30632316","id":"PMC_30632316","title":"RNA-Seq detects a SAMD12-EXT1 fusion transcript and leads to the discovery of an EXT1 deletion in a child with multiple osteochondromas.","date":"2019","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/30632316","citation_count":15,"is_preprint":false},{"pmid":"31646576","id":"PMC_31646576","title":"LncRNA SAMD12-AS1 down-regulates P53 to promote malignant progression of glioma.","date":"2019","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31646576","citation_count":14,"is_preprint":false},{"pmid":"33040085","id":"PMC_33040085","title":"DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A.","date":"2020","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33040085","citation_count":13,"is_preprint":false},{"pmid":"33681653","id":"PMC_33681653","title":"Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion.","date":"2021","source":"Epilepsia open","url":"https://pubmed.ncbi.nlm.nih.gov/33681653","citation_count":13,"is_preprint":false},{"pmid":"32174879","id":"PMC_32174879","title":"TTTCA Repeat Expansion of SAMD12 in a New Benign Adult Familial Myoclonic Epilepsy Pedigree.","date":"2020","source":"Frontiers in neurology","url":"https://pubmed.ncbi.nlm.nih.gov/32174879","citation_count":9,"is_preprint":false},{"pmid":"33501421","id":"PMC_33501421","title":"Genomic analysis of patients in a South Indian Community with autosomal dominant cortical tremor, myoclonus and epilepsy suggests a founder repeat expansion mutation in the SAMD12 gene.","date":"2020","source":"Brain communications","url":"https://pubmed.ncbi.nlm.nih.gov/33501421","citation_count":9,"is_preprint":false},{"pmid":"37228062","id":"PMC_37228062","title":"Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma.","date":"2023","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/37228062","citation_count":6,"is_preprint":false},{"pmid":"36052283","id":"PMC_36052283","title":"LncRNA SAMD12-AS1 Suppresses Proliferation and Migration of Hepatocellular Carcinoma via p53 Signaling Pathway.","date":"2022","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36052283","citation_count":3,"is_preprint":false},{"pmid":"37890330","id":"PMC_37890330","title":"Generation of an induced pluripotent stem cell line (ZJUi013-A) from a Familial cortical myoclonic tremor with epilepsy type 1 patient carrying (TTTCA)n insertion in the SAMD12 gene.","date":"2023","source":"Stem cell research","url":"https://pubmed.ncbi.nlm.nih.gov/37890330","citation_count":0,"is_preprint":false},{"pmid":"40010432","id":"PMC_40010432","title":"SAMD12 as a Master Regulator of MAP4Ks by Decoupling Kinases From the CNKSR2 Scaffold.","date":"2025","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/40010432","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10134,"output_tokens":1164,"usd":0.023931},"stage2":{"model":"claude-opus-4-6","input_tokens":4385,"output_tokens":1247,"usd":0.07965},"total_usd":0.103581,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"Intronic TTTCA and TTTTA pentanucleotide repeat expansions in intron 4 of SAMD12 are the causative mutations for familial cortical myoclonic tremor with epilepsy (FCMTE/BAFME1), identified by long-read sequencing and validated by repeat-primed PCR with co-segregation in affected pedigrees.\",\n      \"method\": \"Long-read sequencing (PacBio/Oxford Nanopore), repeat-primed PCR, long-range PCR, co-segregation analysis\",\n      \"journal\": \"Journal of medical genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — independently replicated across multiple labs and populations (Chinese, Japanese) with multiple orthogonal methods\",\n      \"pmids\": [\"30194086\", \"29939203\", \"30559482\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SAMD12 protein binds to CNKSR1/2/3 scaffold proteins with exceptionally strong affinity and competitively displaces MAP4K kinases (MAP4K4, MINK1, TNIK) from CNKSR1/2/3 scaffolds, thereby decoupling these kinases from their scaffold and inhibiting TNIK activity; ectopic expression of SAMD12 alters neuronal synapse development through this mechanism.\",\n      \"method\": \"Protein interaction characterization (binding affinity measurements), competitive displacement assays, ectopic expression with synapse development readout\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — single lab with multiple biochemical methods and functional cellular readout, but not yet independently replicated\",\n      \"pmids\": [\"40010432\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CNKSR2 acts as both a scaffold and an activator of TNIK during neuronal synapse development, and SAMD12 can inhibit TNIK activity by dissociating TNIK from the CNKSR2 complex.\",\n      \"method\": \"Biochemical interaction assays, ectopic expression, synapse development functional assays\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — single lab with multiple orthogonal methods demonstrating mechanistic pathway placement\",\n      \"pmids\": [\"40010432\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"miR-106a-5p derived from liver fibrosis exosomes targets SAMD12, and knockdown of SAMD12 in liver cancer cell lines exacerbates cell proliferation, indicating SAMD12 suppresses hepatocellular carcinoma cell growth.\",\n      \"method\": \"In vitro knockdown with proliferation assay, in vivo validation\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, KD with cellular phenotype but limited mechanistic pathway detail for SAMD12 protein itself\",\n      \"pmids\": [\"37228062\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The SAMD12 TTTCA/TTTTA repeat expansion mutant allele is unstable and can undergo both contraction and expansion upon intergenerational transmission, with allele sizes varying in repeat copy number between generations.\",\n      \"method\": \"PacBio sequencing of long-range PCR products, repeat-primed PCR\",\n      \"journal\": \"Epilepsia open\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct sequencing of alleles across generations demonstrating instability\",\n      \"pmids\": [\"33681653\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SAMD12 is a sterile alpha motif domain-containing protein whose intronic TTTCA/TTTTA pentanucleotide repeat expansion causes familial adult myoclonic epilepsy (BAFME1/FCMTE1); at the protein level, SAMD12 functions as a master regulator of MAP4K kinases (TNIK, MINK1, MAP4K4) by binding CNKSR1/2/3 scaffold proteins with high affinity, competitively displacing MAP4Ks from these scaffolds to inhibit kinase activity and thereby modulate neuronal synapse development.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SAMD12 is a sterile alpha motif domain-containing protein that functions as a negative regulator of MAP4K kinase signaling at neuronal synapses. SAMD12 binds CNKSR1/2/3 scaffold proteins with high affinity and competitively displaces MAP4K kinases (MAP4K4, MINK1, TNIK) from these scaffolds, thereby inhibiting TNIK activity and modulating synapse development [PMID:40010432]. Intronic TTTCA and TTTTA pentanucleotide repeat expansions in SAMD12 cause familial cortical myoclonic tremor with epilepsy (BAFME1/FCMTE1), with the expanded repeat alleles exhibiting intergenerational instability [PMID:30194086, PMID:33681653].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"The genetic basis of BAFME1/FCMTE1 was resolved: intronic pentanucleotide repeat expansions in SAMD12 were identified as the causative mutations, establishing this gene as the disease locus after years of linkage studies had narrowed the interval.\",\n      \"evidence\": \"Long-read sequencing (PacBio/Nanopore), repeat-primed PCR, and co-segregation analysis across multiple affected pedigrees in Chinese and Japanese cohorts\",\n      \"pmids\": [\"30194086\", \"29939203\", \"30559482\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether pathogenesis is driven by RNA toxicity from repeat transcripts, loss of SAMD12 protein function, or both remains unresolved\",\n        \"No mechanism linking the repeat expansion to cortical myoclonus or epileptogenesis was established\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The SAMD12 repeat expansion was shown to be meiotically unstable, undergoing both contraction and expansion across generations, providing a molecular basis for variable clinical severity and anticipation observed in BAFME1 families.\",\n      \"evidence\": \"PacBio sequencing of long-range PCR products across parent-offspring transmissions\",\n      \"pmids\": [\"33681653\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The relationship between repeat length and disease severity or age of onset was not quantitatively defined\",\n        \"Somatic mosaicism of repeat length in brain tissue has not been characterized\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The first protein-level function of SAMD12 was established: it acts as a competitive inhibitor of MAP4K kinase–scaffold interactions by binding CNKSR1/2/3 with high affinity and displacing TNIK/MINK1/MAP4K4, with functional consequences for neuronal synapse development.\",\n      \"evidence\": \"Binding affinity measurements, competitive displacement assays, and ectopic expression with synapse development readouts in a single-lab study\",\n      \"pmids\": [\"40010432\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Independent replication of the SAMD12–CNKSR competitive displacement mechanism has not been reported\",\n        \"Whether SAMD12 loss-of-function (as might occur from repeat expansion) dysregulates TNIK signaling in patient neurons is untested\",\n        \"Structural basis of the high-affinity SAMD12–CNKSR interaction is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A critical open question is whether the BAFME1-associated repeat expansion causes disease through loss of SAMD12 protein function (and consequent derepression of MAP4K/TNIK signaling), RNA gain-of-function toxicity, or a combination of both mechanisms.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No animal model recapitulating both the repeat expansion and BAFME1 phenotype has been reported\",\n        \"SAMD12 protein levels and TNIK activity have not been measured in patient-derived neurons\",\n        \"The endogenous expression pattern of SAMD12 in human brain regions relevant to BAFME1 is poorly characterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CNKSR1\", \"CNKSR2\", \"CNKSR3\", \"TNIK\", \"MINK1\", \"MAP4K4\"],\n    \"other_free_text\": []\n  }\n}\n```"}